tbuckley/cabot-search huggingface dataset:
Abstract 14888: Arrhythmogenic Right Ventricular Cardiomyopathy-Brugada Syndrome Overlap: A Rare Clinical Entity
Authors: Koushik Sanku, Vindhya Sriramoju, tharun bandarupalli, Vijay Ramu
Journal: Circulation (2022)

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) and Brugada syndrome (BS) are inherited disorders that predispose individuals to arrhythmic sudden cardiac death. ARVC is a heart muscle disorder of intercellular junctions resulting from mutations of desmosomal (DS) genes, often leading to heart failure, and monomorphic ventricular tachycardia (VT). BS is a channelopathy due to sodium channel mutations, usually presenting as polymorphic VT without cardiomyopathy. Case presentation: A 35-year-old male with history of migraines presented with syncope resulting in a fall. No family history of arrhythmias or sudden cardiac death. Initial EKG showed wide complex monomorphic VT. Repeat EKG (figure 1), revealed coved ST-segment elevations in V1, V2 consistent with Brugada type 1 pattern. Emergent coronary angiography was unremarkable, and echocardiogram showed left ventricular ejection fraction of 55-60%, right ventricle (RV) outflow tract proximal diameter measured 3.5cm and normal RV function. An implantable cardioverter-defibrillator (ICD) was implanted for secondary prevention. Device interrogation on follow-up showed 11 shocks for recurrent episodes of monomorphic VT and patient was started on quinidine maintenance therapy. He remained symptom-free on subsequent visits. Genetic testing was positive for DSC2, DSP, and TMEM43 mutations associated with ARVC, but negative for genes associated with BS. Cardiac MRI results are pending. Discussion: Our patient has overlapping features of ARVC (genotype and monomorphic VT) and BS (EKG with coved ST elevations in V1, V2). Emerging evidence supports the theory that defects in DS proteins may affect the integrity of voltage-gated sodium channels in cardiac intercalated discs, leading to BS like phenotype. Conclusion: ARVC and BS could be related to the same disease spectrum, but further studies are required to understand pathophysiology, to guide treatment decisions.
Abstract 14916: Computerized Working Memory Training for Hypertensive Individuals With Executive Function Impairment: A Randomized Clinical Trial
Authors: Regina S Paradela, Brenno Cabella, Mariana P Nucci, Naomi V Ferreira, Laura A Torres, Luiza M Martino, Fernanda M Consolim-Colombo, Danielle I da Costa, Maria Claudia Irigoyen
Journal: Circulation (2022)

Introduction: Hypertension is a risk factor for working memory (WM) impairment, and the Cogmed training has been tested as a non-pharmacological alternative to WM rehabilitation. However, the benefits of Cogmed for the hypertensive population are unknown. Therefore, we aimed to evaluate Cogmed’s effects on WM performance of hypertensive individuals with executive function (EF) impairment. Methods: We included 40 hypertensive patients (aged 40 to 70 years, 68% female) with EF impairment. They were randomized in a 1:1 ratio to receive ten weeks of adaptive Cogmed training or a non-adaptive control training based on online games. The primary outcome was the WM performance. The secondary outcomes were the performance in other neuropsychological tests, as well as the indirect neuronal activity measured using functional magnetic resonance imaging (fMRI) under two WM task conditions: low (memorization of 4 spatial locations) and high (memorization of 6 spatial locations). An intention-to-treat (ITT) and per-protocol (PP) analysis were performed. The fMRI images were evaluated with the FSL tools. Cognitive outcomes were analyzed with a mixed model for repeated measures. Results: Compared to the control group, the Cogmed group did not show significant improvement in WM or any other cognitive outcome post-training (ITT and PP analysis). However, under the WM-low load and WM-high load conditions, respectively, the Cogmed group had an activation decrease in the right superior parietal lobe (ITT and PP analysis) and left inferior frontal lobe (PP analysis) in comparison to the control group (p&lt;0.05). Conclusions: The Cogmed showed no effects on WM performance of hypertensive individuals with EF impairment. However, activation decreases were observed in frontoparietal areas related to the WM network, suggesting intervention-related increases in neural efficiency.
Abstract 14850: Effect of Therapeutic-Dose Heparin on Acute Kidney Injury in Non-Critically Ill Hospitalized Patients With Covid-19: The Activ4a and Attac Randomized Trial
Authors: Nathaniel Smilowitz, Erinn Hade, Lucy Kornblith, Lana Castellucci, Mary Cushman, Michael E Farkouh, Beverly Hunt, Keri Kim, Andrei Kindzelski, Patrick R Lawler, Eric Leifer, Bryan J McVerry, Harmony Reynolds, Judith Hochman, Judith S Hochman, Matthew D Neal, MD, Jeffrey S Berger
Journal: Circulation (2022)

Background: Acute kidney injury (AKI) is common in patients with COVID-19 and mediated, in part, by thromboinflammation. In non-critically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in non-critically ill patients hospitalized for COVID-19. Methods: Non-critically ill patients hospitalized for COVID-19 were enrolled in an open-label, multiplatform randomized trial of therapeutic-dose heparin versus usual-care pharmacologic thromboprophylaxis. The primary endpoint of this analysis was in-hospital diagnosis of AKI or death. AKI was defined as Kidney Disease Improving Global Outcomes stage 2 or 3 AKI (≥2-fold increase in serum creatinine or initiation of renal replacement therapy). A Bayesian statistical model estimated the risk of AKI or death between those randomized to therapeutic-dose anticoagulation versus usual-care thromboprophylaxis, adjusted for age, sex, D-dimer, time epoch, country, site, and platform. Results: Among 1922 enrolled from ACTIV4a and ATTACC, 23 were excluded due to ESRD at enrollment. Baseline or follow-up creatinine was missing for 205 individuals. Among 1694 participants analyzed, median age was 60, 58% were men, and median baseline creatinine was 0.9 mg/dL. The primary endpoint occurred in 83 participants (4.9%); 4.4% assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR] 0.72, 95% CrI 0.47-1.10; posterior probability of superiority [defined as relative risk &lt; 1.0] was 93.6%). Therapeutic-dose anticoagulation was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs. 4.6%; aRR 0.64, 95% CrI 0.40-0.99) compared to usual-care thromboprophylaxis. Conclusions: Therapeutic-dose anticoagulation with heparin was associated with a high probability of superiority to reduce the incidence of in-hospital stage 3 AKI or death in non-critically ill patients hospitalized for COVID-19, compared with usual-care thromboprophylaxis.
Abstract 15008: Hydrogel-Mediated Sustained Intra-Pericardial Delivery of Endothelial Colony-Forming Cells-Derived Extracellular Vesicles Promote Cardiac Repair Post-Myocardial Infarction
Authors: Karina P Gomes, Maia Ross, Anshul S Jadli, Nadia DiMarzo, Darrell D Belke, Paul W Fedak, Vaibhav B Patel
Journal: Circulation (2022)

Introduction: Myocardial infarction (MI) is a leading cause of death worldwide. Although available treatments improve prognosis post-MI, they do not remediate cardiomyocyte death and loss of cardiac vasculature, resulting in chronic maladaptive remodeling and subsequently, heart failure. Extracellular vesicles (EVs) derived from endothelial colony-forming cells (ECFCs) show therapeutic potential, facilitating adaptive cardiac remodeling post-MI. However, ECFCs function is compromised in patients with type-2 diabetes, a common risk factor for MI, limiting the applicability of autologous cell-based therapies. Therapeutic administration is a further challenge, as current strategies present difficulties regarding invasiveness, retention, and efficacy. Hypothesis: We hypothesized that the minimally invasive intra-pericardial (IP) injection of ECFCs-EVs within a hydrogel would improve cardiac retention and promote sustained therapeutic release, facilitating cardiac repair in a murine model of MI. We anticipated that this repair would be greater with the use of EVs derived from wildtype mice than from diabetic mice. Methods: The impact of wildtype and diabetic ECFCs-EVs was evaluated on both in vitro EVs retention and angiogenesis. In a murine model of MI, the left anterior descending coronary artery was ligated while the pericardium was preserved. We evaluated whether IP injection is an effective and safe method of delivering hydrogels containing ECFCs-EVs, in addition to its long-term effects on cardiac morphology and function. Results: Our findings indicate that hydrogel use facilitates sustained EVs release. Besides that, the administration of ECFCs-EVs increased coronary endothelial cell proliferation, migration, and vascularization in vitro, and reduced maladaptive cardiac remodeling, improving cardiac contractility and function in vivo. These effects appear to be more pronounced with the administration of wildtype ECFCs-EVs. Conclusions: Collectively, our results underscore the therapeutic promise of ECFCs-EVs to improve cardiac repair after MI.
Abstract 14924: Gender Differences in Cardiac Rehabilitation Participation and Outcomes in a National Medicare Sample: An Instrumental Variable Approach
Authors: Christina Thaler, Hechuan Hou, Devraj Sukul, Steven J KETEYIAN, Angela Quain, Michael Joynt, Jeffrey McCullough, Mike P Thompson
Journal: Circulation (2022)

Background: Cardiac rehabilitation (CR) participation following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) decreases patient morbidity and mortality. Many studies are underpowered to evaluate gender differences. We aimed to look at gender differences in CR use and short term outcomes including 1-year mortality in a national Medicare sample. Methods: We identified Medicare beneficiaries over 65 years undergoing PCI and CABG from 07/2016-12/2018. Primary exposures included female vs. male sex and CR use within one year of discharge based on outpatient claims. Clinical outcomes included 1-year mortality and readmissions. We analyzed differences in characteristics, CR use, and associated outcomes between females and males using multivariable and instrumental variable analyses using distance to CR facility as the instrument. Results: 414,730 beneficiaries underwent PCI and CABG, of which 145,512 (35.1%) were female. Females were more likely to be older, Black race, dual eligible, live in distressed communities, and have a CR facility in their zip code, and were less likely to be Hispanic, elective procedures, or undergo CABG. CR use was lower for females than males (32.2% vs. 40.5%, p&lt;0.001), which remained significant after adjustment for patient covariates (OR=0.91, 95% CI: 0.89-0.92, p&lt;0.001). One-year mortality for CR users vs. non-CR users was 2.1% / 2.4% and 15.4% / 14.5% for women and men, respectively. One-year readmissions for CR users and non users was 34.3% / 31.2% and 52.8% / 45.0% for women and men, respectively. The adjusted and IV-adjusted average absolute effect of CR use on mortality was similar for females and males but was stronger on 1-year readmissions for females vs. males (Figure). Conclusion: Female Medicare beneficiaries attend CR following PCI and CABG at lower rates than men, but have increased benefit with CR participation on 1-year readmissions with similar mortality benefit relative to men.
Abstract 14768: Contemporary Hospitalization and Thirty-Day Readmission Rates of Unstable Angina in the United States: Insights From Nationwide Readmissions Database 2016-2019
Authors: Ilhwan Yeo, Ming Zhong, Sun-Joo Jang, Robert M Minutello, Tara Shah
Journal: Circulation (2022)

Introduction: There are limited data on the contemporary hospitalization rate and 30-day readmission characteristics of unstable angina (UA). Methods: Using Nationwide Readmissions Database from 2016 to 2019, we identified UA hospitalizations based on ICD-10-CM codes and analyzed the rate, trend, timing, causes, and costs of 30-day readmissions after UA in the United States. Multivariable regression analysis was conducted to determine the predictors of 30-day readmission. Results: A total of 498,008 patients were hospitalized with UA, resulting in the in-hospital mortality of 0.4%. During the study period, a significant decrease in the temporal trend of UA hospitalization rate was observed ( Figure 1 ). Among 458,823 patients who were discharged alive, 11.4% were readmitted within 30 days with a median time to readmission of 9 days. There was a significant reduction in the temporal trend of 30-day readmission rate ( Figure 2 ). The most common cause of readmission and procedure during the readmission were recurrent UA and left heart catheterization, respectively. While cardiovascular comorbidities, including congestive heart failure and atrial fibrillation, were associated with an increased likelihood of 30-day readmission, the ischemic evaluation performed during index hospitalization was associated with decreased odds of readmission ( Table ). The mortality during the readmission was 2%. The cumulative costs of hospitalization were $30,729 vs. $14,998 for UA patients with and without readmission, respectively. Conclusions: The index hospitalization and early readmission rates of UA have decreased over time. About 1/10 of UA patients were readmitted within 30 days of discharge, primarily due to recurrent UA. The early readmission may be reduced by a timely ischemic evaluation following UA.
Abstract 14870: Adrenomedullin in Patients With Out-of-Hospital Cardiac Arrest
Authors: Thomas A Zelniker, Dominik Schwall, Fardin Hamidi, Simone Steinbach, Pascal Scheller, Sebastian Spaich, Evangelos Giannitsis, Hugo A Katus, Norbert Frey, Michael R Preusch
Journal: Circulation (2022)

Introduction: Adrenomedullin (ADM) is a free circulating peptide that regulates endothelial barrier function and vascular tone. Here, we sought to study the relationship of adrenomedullin in combination with lactate and the risk of death in patients with out-of-hospital cardiac arrest (OHCA) of non-traumatic origin. Methods: Mid-regional pro-ADM (MR-proADM) concentrations were measured in OHCA patients after successful ROSC on admission. The outcome of interest was all-cause death. Patients were characterized by quartiles (Q) of MR-proADM and lactate concentrations. Cox models were adjusted for age, sex, shockable rhythm, bystander resuscitation, and baseline eGFR. Results: A total of 232 patients were included in the present study (28% women, 67 years, SAPS II score 80). In total, 132 patients (56.9%) died, and 24 patients had an unfavorable neurologic outcome (i.e., a CPC score of 3-4). The median MR-proADM and lactate levels were 1.4 nmol/L (IQR 0.8 to 2.8 nmol/L) and 4.8 mmol/L (IQR 2.8 to 7.4 mmol/L), respectively. MR-proADM concentrations correlated weakly with lactate levels (r=0.23, P&lt;0.001). High (Q4) versus low (Q1-Q3) MR-proADM concentration was associated with an increased rate of death at 28 days (45.4% vs. 75.9%; P&lt;0.001; Fig A ). After multivariable adjustment (including baseline lactate levels), higher MR-proADM levels were significantly associated with an increased risk of death (Q4 vs. Q1-Q3: adjusted HR 1.84, 95% CI 1.21 to 2.77; adjusted HR for 1 unit increase in standardized biomarker 1.55, 95% CI 1.28 to 1.86). The combination of high MR-proADM and high lactate (Q4) concentration identified patients at particularly elevated risk (adjusted HR 3.99; 95% CI 1.67-9.56; Fig B ). Conclusions: Higher MR-proADM concentration are associated with an increased risk of death in patients with OHCA of non-traumatic origin. The combination of high MR-proADM and high lactate levels identifies patients at distinctly elevated risk.
Abstract 14931: Frailty Status Modifies the Efficacy of ICD Therapy Among Patients With Chronic Heart Failure With Reduced Ejection Fraction
Authors: Matthew W Segar, Sumitabh Singh, Shyon Parsa, Gordon Reeves, Robert J Mentz, Daniel E Forman, Mehdi Razavi, Mohammad Saeed, Dalane W Kitzman, Ambarish Pandey
Journal: Circulation (2022)

Introduction: Frailty is common in patients with heart failure with reduced ejection fraction (HFrEF) and is independently associated with mortality. Implantable cardiac defibrillator (ICD) therapy is recommended to reduce mortality risk in patients with HFrEF. Whether baseline frailty modifies the efficacy of ICD therapy in HFrEF is not known. Methods: Stable outpatients with HFrEF randomized to ICD vs. placebo in the SCD-HeFT trial were included. Baseline frailty was estimated using Rockwood’s Frailty Index (FI) by dividing the number of deficits present by the number of variables considered (n=37). Participants were categorized into tertiles of FI. Multivariable adjusted Cox proportional hazard models with multiplicative interaction terms (frailty*treatment arm) were constructed to evaluate whether frailty modified the treatment effect of ICD therapy on the primary outcome all-cause mortality and secondary outcomes of cardiovascular (CV) mortality and sudden cardiac death (SCD). Results: Among 1,673 participants (age: 59±12 y, 23% women), the median [IQR] FI ranged from 0.19 [0.14-0.23] in tertile 1 (lower frailty burden) to 0.51 [0.47-0.56] in tertile 3 (higher frailty burden). Baseline frailty significantly modified the treatment effect of ICD therapy (P-interaction: 0.03) ( Fig. A ). Specifically, ICD therapy was associated with a lower risk of all-cause mortality in tertile 1 [HR (95% CI) = 0.55 (0.37-0.80)] but not in tertile 3 participants [HR (95% CI) = 0.90 (0.67-1.22)] ( Fig. B ). Among secondary outcomes, frailty status modified the association of both CV mortality and SCD (P-interaction = 0.007 and 0.04, respectively). Similar results were observed in landmark analyses at 12 months. Conclusions: Among patients with chronic stable HFrEF, baseline frailty modified the treatment effect of ICD therapy with a greater reduction in the risk of CV mortality and SCD in patients with a lower burden of frailty.
Abstract 15030: Hidden Sources of Inequity in Heart Failure Care Transitions: A Mixed-Method Network Analysis of Clinical Notes
Authors: Sijia Wei, Eleanor McConnell, Kirsten N Corazzini, James Moody, Wei Pan, Bradi B Granger
Journal: Circulation (2022)

Introduction: Fragmentation in heart failure (HF) care transitions occur disproportionately among those adversely affected by social drivers of health. Social network analysis (SNA) may provide new insights into barriers to equitable care. Purpose: To assess the nature and structure of clinician networks across health system settings of care during care transitions. Methods: An explanatory sequential mixed-methods design was used. We stratified a purposeful sample (n=11) from a cohort of adults (n=1269) first hospitalized for HF between 2016 and 2018 by race, Medicaid use, and Area Deprivation Index, adjusting for risk (3M Clinical Risk Groups Severity of Illness Score and Charlson Comorbidity Index). EHR clinical notes were used to construct patients' clinician networks 1-year before, during, and after the index hospitalization using patient-sharing (2-mode) SNA. Patients' clinician positional and structural network measures were integrated with qualitative analyses of clinical notes. Results: Socioeconomically advantaged patients used fewer acute care services and lived longer. They tended to have higher network density and clinicians more centrally located in the health system network earlier and across settings and frequent telephone notes between visits that indicated reciprocal communication patterns among patients and clinicians shown in contents. Close care relationships and early involvement of influential providers measured by high Eigenvector centrality may be vital for smooth care transitions. Conclusions: Barriers to care coordination may result from variability in clinician networks. Well-connected clinician teams and consistent and reciprocal communication between patients and outpatient care teams are associated with more effective care coordination. Patients with clinicians in central and bridge positions within a health system network may receive higher quality care due to greater social capital and influence.
Abstract 14787: Quantification of Flow and Biomechanics by Echocardiography (echo) in the Fetal Single Ventricle (sv)
Authors: Brett A Meyers, Sayantan Bhattacharya, Melissa Brindise, Yue-Hin Loke, Ronald M Payne, Pavlos Vlachos
Journal: Circulation (2022)

Introduction: Echo-based ventricular flow and biomechanical analysis provides novel measurements of SV function that can be assessed serially. However, this analysis has not been applied to clinical studies. This study demonstrates a new workflow to measure ventricular flow and biomechanics from apical 4-chamber imaging for hypoplastic left heart syndrome [HLHS] patients and age-matched controls. Methods: We retrospectively collected echos at 33 weeks gestation prenatally and 7 days post-birth postnatally. Color Doppler echo of the LV/RV were evaluated using an in-house vector flow reconstruction algorithm, quantifying energy loss [EL] and vortex strength [VS]. B-mode echo of the LV/RV were evaluated for parameters including cardiac output [CO] and global longitudinal strain [GLS]. Results: 9 HLHS subjects and 11 age-matched controls were included. Prenatal HLHS patients exhibited elevated CO, EL, and VS (p&lt;0.01) but proportional GLS compared to the control LV/RV. The parameters serially increased postnatally (p&lt;0.01), consistent with transitional physiology. GLS in HLHS was differentiable from the normal RV only in postnatal studies, resembling normal LV values. Conclusions: Altered ventricular flow and biomechanics were observed for HLHS patients compared to controls during early life. These novel parameters can be serially evaluated using conventional echo imaging. We will perform longitudinal studies of this HLHS cohort as they progress through surgical palliation to fully understand how our integrated workflow can better inform SV patient care. Figure 1: Left – Comparison of ventricular flow and biomechanical markers between HLHS and control subjects, for prenatal (fetal) and postnatal (neonatal) ages. Right – Ventricular flow patterns for HLHS and control subjects for different ages.